Antimicrobial nail coating composition

ABSTRACT

Antimicrobial nail coating compositions, and methods for treating and preventing microbial infections of the nail area, are provided. The antimicrobial nail coating compositions can be used to treat and/or prevent infections caused by microbes including bacteria, molds, spores, viruses and fungi, while providing a nail coating having acceptable handling and esthetic qualities. The compositions can include alcohol-containing solvents, and, as antimicrobial agents, quaternary amines or phenols.

This application is a division of U.S. application Ser. No. 09/006,811,filed Jan. 14, 1998, which is a continuation-in-part of U.S. applicationSer. No. 08/993,464, filed Dec. 18, 1997 and now abandoned, which is acontinuation-in-part of U.S. application Ser. No. 08/756,958, filed Dec.3, 1996 and now U.S. Pat. No. 5,827,870.

FIELD OF THE INVENTION

The present invention relates to antimicrobial nail coatingcompositions, and to methods for preparing and using those compositions.In particular, the present invention relates to antimicrobial nailcoating compositions useful in treating and preventing the spread ofinfections of the nail area caused by bacteria, fungi and othermicrobes.

BACKGROUND OF THE INVENTION

Nail coatings for cosmetic purposes, known variously as base coats, topcoats, lacquers, varnishes, and enamels are the largest and mostimportant group of manicure preparations. "The Nails", Chapter 22 inHarry's Cosmeticology, Wilkinson, J. B., and Moore, R. J., Eds., 7thEdition, pp 369-393. Chemical Publishing Company, Inc., New York, N.Y.1982. Although nail coatings are generally collectively referred to as"nail polishes", such nomenclature is erroneous. Polishes contain fineabrasives that impart desirable characteristics, such as smoothness,based on friction created by buffing. Nail coatings, on the other hand,impart similar characteristics without friction due to componentscontained therein.

It is preferable that nail coatings be easily applied, dry rapidly anduniformly, convey a high luster upon drying, and be substantiallynon-toxic. The application process can be messy and time consuming.Thus, it is also desirable that such coatings be durable to avoidfrequent applications. Other desirable characteristics of nail coatingsinclude smooth and even flow on application and uniform drying withoutadverse surface artifacts.

The vast majority of nail coating systems currently in use containeither toluene or formaldehyde, or a combination of toluene and/orformaldehyde with aryl resins. Toluene and formaldehyde have anextremely unpleasant odor, are toxic by ingestion or absorption throughthe skin, and can easily sensitize the skin, leading tohypersensitivity. Aldehydes are also immunoreactive agents, which canpromote inflammation and cause desiccation of vital tissue. Furthermore,toluene and formaldehyde have been recently recognized as carcinogens byCAL OSHA and other health and safety regulatory agencies (See, e.g.,United States Department of Labor OSHA Standard Subpart Z 1910.1048).Thus, it is desirable to minimize or eliminate toluene and aldehydes,particularly formaldehyde, from nail coating formulations.

In part due to the inherent high volatility and enhanced evaporationcoefficients of nail coatings, moisture and organic contaminants such asbacteria, molds, spores, viruses and fungi can become trapped on thenail surface and between the nail coating and the nail plate, resultingin polymicrobial infections of the nail plate and brittle, unsightly,disfigured nails. Onychomycosis is just one example of the myriad ofmicrobial etiologies of nail disfigurement. Treatment of polymicrobialinfections of the nail plate can require expensive, prolonged medicaltherapy, which is not always innocuous and can even be toxic. Moreover,such treatments often provide less than satisfactory cure rates andpatient tolerance. From a commercial standpoint, professional nailtechnicians and consumers of professional nail care products andservices recognize that lifting and chipping of artificial (e.g.acrylic) nails is exacerbated by organic contaminants that grow at theinterface of the natural nail and the artificial nail, or the artificialnail-coating interface. In addition, organic contaminants between thesurface of the natural nail and a lacquer coating can cause lifting,chipping and reduced adhesion of lacquer coatings.

U.S. Pat. No. 4,957,730 discloses an antimycotic nail varnish. The nailvarnish comprises, as anti-mycotic agents, certain 1-hydroxy-pyridones.However, the 1-hydroxy-pyridones have limited application because theyare effective against mycotic organisms, not bacteria. Thus, in order totreat bacterial infections, an antibacterial agent would need to besomehow incorporated into these formulations. U.S. Pat. No. 5,487,776discloses an anti-fungal nail lacquer and method for use thereof. Theanti-fungal nail lacquer contains, as an anti-fungal agent,griseofulvin. However, griseofulvin, like the 1-hydroxy-pyridones ofU.S. Pat. No. 4,957,730, is an anti-fungal agent and an additionalantibacterial agent is required in order to treat bacterial infections.Furthermore, the disclosure provides that about 25 to 75 percent of thegriseofulvin will generally be in solution, while the remaining 75 to 25percent will generally be in colloidal suspension.

While alcohols are commonly used as solvents in nail lacquercompositions, prolonged contact between many antimicrobial agents canresult in diminished activity of the antimicrobial agent. Clearly itwould be advantageous, for esthetic reasons and for consistency inapplication, to have a true solution of an antimicrobial agent in a naillacquer composition. It would also be advantageous if a nail lacquercomposition were developed that provided both treatment and prophylaxisagainst a broad spectrum of microorganisms.

Thus, there remains a need for prophylaxis against polymicrobialinfections of the nail plate, including continuous prophylaxis againstacquired organic contamination after the application of a nail coating.It is also desirable to minimize or eliminate aldehyde and ketonesolvents, particularly formaldehyde, in nail coatings. The presentinvention is directed to these, as well as other, important needs.

SUMMARY OF THE INVENTION

One aspect of the present invention provides an antimicrobial nailcoating composition comprising an organic solvent, at least onefilm-forming polymer or resin, and an antimicrobial agent. Suitableantimicrobial agents for use in compositions of the present inventioninclude, but are not limited to, antimicrobial quaternary amines andhomologs thereof. Other similarly active, soluble antimicrobial agentsknown in the art can be used in compositions of the present invention.

Another aspect of the present invention is a method for treatingmicrobial infections of the nail plate comprising applying to the nailarea an antimicrobial nail coating composition comprising an organicsolvent, at least one film-forming polymer or resin, and anantimicrobial agent.

A further aspect of the present invention is a method for preventing thespread of microbial infections of the nail plate comprising applying tothe nail area an antimicrobial nail coating composition comprising anorganic solvent, at least one film-forming polymer or resin, and anantimicrobial agent.

Additional features and embodiments of the present invention will becomeapparent to those skilled in the art in view of the ensuing disclosureand appended claims.

DETAILED DESCRIPTION OF THE INVENTION

It has been discovered that antimicrobial compositions containingantimicrobial agents, including quaternary amines and/or relatedhomologs, can be advantageously incorporated within nail coatings toprovide prophylaxis against susceptible organic contaminants. Inconnection with the present invention, it has further been surprisinglyand unexpectedly found that antimicrobial agents having aminefunctionalities, such as quaternary amines, including benzalkoniumchlorides, can form a solution in alcohol-containing solvents withoutbecoming deactivated during storage.

The present invention provides antimicrobial compositions for nailcoatings, and methods for manufacturing and using these compositions.The antimicrobial compositions of the present invention are intended foruse on vertebrate nail plates, and present a useful means of immediatedecontamination and extended prophylaxis against polymicrobialinfections of the nail plate. The antimicrobial composition of thepresent invention may be formulated into basecoats and topcoats asdefined herein. The compositions contain at least one antimicrobialagent, preferably a quaternary amine and/or at least one antimicrobiallyactive homologue thereof.

The compositions of the present invention are intended as non-aqueousnail coatings, and generally contain typical components known in the artfor use in non-aqueous nail coatings. As used herein, the term"non-aqueous" means containing less than 5 weight percent water,preferably less than 2 weight percent, and more preferably less than 1weight percent. Quantities presented herein as "percent by weight" or"weight percent" refer to the percent of a particular component in acomposition based on the total weight of the composition.

Antimicrobial agents that can be incorporated into the compositions ofthe present invention include agents that are commonly used for suchapplications and are chemically compatible with other components presentin the nail coating compositions. Exemplary suitable antimicrobialagents for use in the present invention include quaternary amines, andphenol derivatives such as parachlorometaxylenol. Preferredantimicrobial agents are quaternary amines, and more preferred arebenzalkonium chlorides (BAC), including antimicrobially active homologsthereof.

Antimicrobial agents used in the compositions of the present inventionare advantageously employed at concentrations known to beantimicrobially effective on hard surfaces, e.g., agents commonly usedin counter-top disinfectant formulations. Such antimicrobial agents aregenerally of low volatility, such that they are not lost by evaporation,and are retained in both the fluid and solid states of the compositions.For purposes of the present invention, the antimicrobial activity of theagents preferably remains substantially unchanged following transitionof a nail coating composition from the fluid to the solid state, i.e.,polymerization/solidification (see Table II, infra).

Antimicrobial agents are incorporated into the nail coating compositionsof the present invention at a concentration of from about 0.05 percentto about 5 percent by weight, preferably from about 0.1 percent to about2.5 percent by weight, and more preferably from about 0.3 percent toabout 1 percent by weight. These quantities refer to the total amount ofantimicrobial agent present in the composition, and can include one ormore antimicrobial agents.

In preferred embodiments of the present invention, the antimicrobialnail coating compositions include a benzalkonium chloride (BAC)compound. The BAC can be in the form of a mixture of homologs, such asthat defined by the United States Pharmacopaeia, or of an individualhomolog.

Benzalkonium chlorides suitable for use in the compositions and methodsof the present invention have the general formula (I) ##STR1## wherein Ris an alkyl group having from 1 to 24 carbon atoms, commonly from 5 to20 carbon atoms, preferably from 10 to 17 carbon atoms, more preferablyfrom 10 to 15 carbon atoms, and even more preferably from 12 to 14carbon atoms. In certain preferred embodiments, single homologs ofbenzalkonium chlorides, rather than mixtures thereof, are used as theantimicrobial agents in the compositions and methods of the presentinvention.

When BAC is used as the antimicrobial agent, or part thereof, in acomposition of the present invention, the BAC homologs having theformula (I) will preferably constitute at least about 50 percent byweight, preferably at least about 75 percent by weight, more preferablyat least about 90 percent by weight and most preferably at least about95 percent by weight, of the antimicrobial agent. Most preferred for usein the compositions of the present invention are preferred BAC homologscontaining alkyl groups (R) of 12, 13 or 14 carbon atoms.

Exemplary suitable BAC homologs, that may be used singly or incombination according to the present invention, includeN,N-dimethyldecyl ammonium chloride, N,N-dimethyl-undecyl ammoniumchloride, N,N-dimethyl-dodecyl-ammonium chloride,N,N-dimethyltridecylammonium chloride, N,N-dimethyl-tetradecylammoniumchloride, N,N-dimethylpentadecylammonium chloride,N,N-dimethyl-hexadecylammonium chloride, and N,N-dimethylhepta-decylammonium chloride.

Other antimicrobial agents that may be used in the compositions of thepresent invention, alone or in combination, include other antimicrobialquaternary amines and related compounds, such as, for example,monoalkyltrimethyl ammonium salts, dialkyl-ammonium salts,heteroaromatic ammonium salts, polysubstituted quaternary ammoniumsalts, bis-quaternary ammonium salts and polymeric quaternary ammoniumsalts.

Other antimicrobial agents, also referred to as germicidal agents, whichmay be used in compositions of the present invention alone or incombination, include phenols, including cresols and resorcinols. Forexample, parachlorometaxylenol is a suitable antimicrobial agent for usein the compositions of the present invention. Phenols, in concentrationsof about 0.2, 1.0, and 1.3 percent by weight are bacteriostatic,bactericidal, and fungicidal, respectively. While it is not intendedthat the present invention be bound by any particular theory, it isbelieved that the germicidal action of phenols at these concentrationsis effected through protein denaturation. The phenol-protein interactionis relatively weak, allowing the phenol molecule to penetrate deeplyinto the tissue. Thus, phenol can penetrate relatively dense, intactkeratinous matrices, such as the stratum corneum or the nail plate.Several phenol derivatives are more potent than phenol itself, and themost important among these are the halogenated phenols and bis-phenols,the alkyl-substituted phenols and the resorcinols.

Examples of resorcinols useful in compositions of the present inventioninclude resorcinol, hexylresorcinol, hexachlorophene, parabens, thymol,chlorothymol, parachlorometaxylenol, orthophenylphenol, p-tertiarybutylphenol, p-tertiaryamylphenol, o-benzylphenyl-p-chlorophenol,parachlorophenol, camphorated parachlorophenol, tetrabromomethylphenol,and 2,6-dimethyl-4-chlorophenol. Resorcinols and other phenoliccompounds may be employed in amounts from about 0.05 percent to about 5percent by weight, preferably from about 0.1 percent to about 2.5percent by weight and more preferably from about 0.3 percent to about 1percent by weight.

Also suitable for use as germicides in the compositions of the presentinvention are antimicrobial biguanides. Biguanides are compatible withBAC formulations and are believed to function by causing cellular deathby the disruption of the cell membrane of an infecting microorganism.Exemplary biguanides suitable for the present invention arechlorhexidine gluconate and its acetate derivative. These compounds maybe employed in the present invention, singly or in combination, inamounts from about 0.05 percent to about 5 percent by weight, preferablyfrom about 0.1 percent to about 4.5 percent by weight and morepreferably from about 1.0 to about 4 percent by weight.

Another class of germicides suitable for use in the compositions of thepresent invention are antimicrobial furan derivatives. The presence of anitro group at the five position of the 2-substituted furans confersantimicrobial activity to this class of compounds. An exemplary furanderivative suitable for use as a germicide according to the presentinvention is nitrofurazone. Furan derivatives may be incorporated intothe present invention at concentrations of from about 0.05 percent toabout 5.0 percent by weight, preferably from about 0.1 percent to about3 percent by weight, and more preferably from about 0.5 percent to about2 percent by weight.

Certain dyes exhibit antimicrobial activity and are suitable for use inthe compositions of the present invention. Examples of suitableantimicrobial dyes include triphenyl-methane hexamethylrosanilinechloride and tetramethylthionine chloride. Antimicrobial dyes may beincorporated into the present invention in concentrations of from about0.01 percent to about 2 percent by weight, preferably from about 0.02percent to about 1.5 percent by weight and more preferably from about0.025 percent to about 1 percent by weight.

Other antimicrobial agents known in the art, that are compatible withthe formulations disclosed herein that contain benzalkonium chlorides orphenol derivatives as antimicrobial agents, are suitable for use in thecompositions of the present invention. Table I lists exemplarypharmacologic compounds that may be used in compositions of the presentinvention. In addition to specific examples of classes of antimicrobialagents in the categories discussed above, those skilled in the art willrecognize that antimicrobial agents outside those categories, and thatare compatible with other components in nail coating compositions, canbe used in compositions of the present invention. Such active agents areeffective against polymicrobial infections by various mechanisms ofaction. Suitable active agents are effective against, for example,infections caused by dermatophytic fungi, yeast, bacteria and molds. Theactive agents listed below, and/or others, can generally be incorporatedinto compositions of the present invention, singly or in combination, inquantities from about 0.05 percent to about 5 percent by weight,preferably from about 0.1 percent to about 2.5 percent by weight, andmore preferably from about 0.3 percent to about 1 percent by weight,with the exact quantity determined in part by the activity and/orcomposition of the antimicrobial agent.

                  TABLE I                                                         ______________________________________                                        Antimicrobial Agents useful in compositions of the                              invention                                                                                    Product                                                        Generic Name Manufacturer                                                   ______________________________________                                        A. Agents used in treating dermatophyte infections                                Amorolfine   Locery        Roche                                            Econazole-nitrate Spectazole Ortho                                            Naftifine Naftin Herbert Labs                                                 Oxiconazole Oxistat Glaxo                                                     Sulconazole Exelderm Westwood-Squibb                                          Terbinafine Lamisil Novartis                                                  Tolnaftate Tinactin Schering-Plough                                           Undecylinic acid Desinex Pharmacraft                                           Gordochrom Gordon Labs                                                       Griseofulvin Fulvicin Schering                                                Itraconazole Sporonox Janssen                                                 Fluconazole Diflucan Pfeizer                                                B. Agent used in treating yeast infections                                        Nystatin     Mycostatin    Westwood-Squibb                                C. Agents used in treating dermatophyte, yeast and                              bacterial infections                                                            Ciclopiroxolamine                                                                          Loprox        Hoechst-Roussel                                  Clotrimazole Lotrimin Schering-Plough                                         Econazole-nitrate Spectazole Ortho                                            Haloprogin Halotex Westwood-Squibb                                            Miconazole Micatin/ Ortho                                                      Fungoid Tincture Pedinol                                                     Quaternium 12 Mone Kenlor Industries                                        D. Agents used in treating nondermatophyte (saprophyte)                         opportunistic infections                                                        Amphotericin B                                                                             Fungizone     Bristol-Myers                                      Squibb                                                                      Ketoconazole Nizoral Janssen                                                  BAC Mycocide NS Woodward Labs                                                 Fluconazole Diflucan Roerig-Pfizer                                            Itraconazole Sporanox Janssen                                               E. Agents used in treating deep (systemic) mycotic                              infections                                                                      Flucytosine  Ancobon       Roche                                          F. Agents used in treating actinomycetes infections                               Amikacin     Amikin        Apothecon                                        Ampicillin Omnipen Wyeth-Ayerst                                                Polycillin Apothecon                                                          Principen Apothecon                                                          Penicillin-G Bicillin Wyeth-Ayerst                                             Wycillin Wyeth-Ayerst                                                        Tetracycline Doxycycline Laderle                                              Trimethoprim Bactrim Roche                                                    Sulfamethoxazole Septra Glaxo-Wellcome                                      ______________________________________                                    

To provide an acceptably functional nail coating, the antimicrobialcompositions of the present invention preferably employ one or more ofthe following components, either alone or in combination: film-formingpolymers, resins, plasticizers, solvents, diluents, colors and/orpigments, ultraviolet light-absorbing agents, suspension and viscosityregulating, vitamins, proteins and/or growth promoters, dryingaccelerators, hardening accelerators, lipids and vitamins.

Film-forming polymers can add thickness and gloss to a nail preparationfollowing polymerization. For use in compositions of the presentinvention, the film formed by polymerization should demonstrate goodadhesion characteristics, and be flexible enough to avoid significantchipping and cracking, as demonstrated by the seven day durability testdescribed by Shansky [Shansky, A. Drug Cosmet. Ind. 123(5):46, 1978.].By "good adhesion" is meant that a coating will display little liftingand/or chipping, preferably substantially no lifting and/or chipping,for about 3 to about 5 days after application to a natural nail and forabout 7 to about 10 days after application to an acrylic nail. Suchfilm-forming polymers are well known to those skilled in the art andinclude such polymers as are generally employed in photoreactions. Typesof film-forming polymers suitable for use in compositions of the presentinvention include cellulose derivatives such as cellulose esters andnitrocellulose, and acrylic polymers. Cellulose derivatives suitable asfilm-forming agents are listed in U.S. Pat. No. 5,516,509, thedisclosure of which is hereby incorporated herein by reference. Specificexamples of suitable film-forming polymers include poly(methylmethacrylate), poly(ethyl methacrylate), poly(butylmethacrylate),cellulose acetate, cellulose acetate propionate, and cellulose acetatebutyrate. In addition to film-forming polymers, the compositions of thepresent invention can include monomers that form a film uponphotopolymerization. Suitable monomers include acrylic monomers such asmethylmethacrylate, ethylmethacrylate, and butylmethacrylate. The amountof film-forming polymer, if used, is from about 5 to about 65 percent byweight, preferably from about 7 percent to about 50 percent by weightand more preferably from about 10 percent to about 30 percent by weight,based on the total weight of the composition and including the weight ofthe monomers.

Resins are typically added to nail coatings to enhance gloss, hardnessand adhesion and decrease susceptibility to detergents. [Wilkinson, J.B., and Moore, R. J., Eds. The Nails. Chapter 22 in Harry'sCosmeticology, 7th Edition, pp 369-393, Chemical Publishing Company,Inc. New York, N.Y. 1982]. Such resins are well known to those skilledin the art, and examples of compatible resins for use in thecompositions of the present invention include shellac, pontianak, andsynthetic resins such as acrylic copolymers, polyvinyl acetate,butyrates and arylsulfonamide-formaldehyde resins. Other resins that arecompatible with the present formulation are melamine formaldehyde, ureaformaldehyde, the styrene alkyds and the family of polyester resins androsin based resins. If desired, nylon solids may be added toformulations for use according to the invention to accelerate the dryingof the resin, and to enhance the film-forming characteristics. Resinsare optional components in the compositions of the present invention,and certain film-forming polymers, such as nitrocellulose, can providesatisfactory adhesion characteristics so that resins are not needed.Suitable concentrations of resins for use in the compositions of thepresent invention are from about 1 percent to about 80 percent byweight, preferably from about 3 percent to about 25 percent by weightand more preferably from about 3.5 percent to about 10 percent byweight. Also preferably, compositions of the present inventioncontaining resins, when dry, have a resin solids content of from about20 percent to about 40 percent by weight.

Plasticizers can be used in nail formulations to decrease brittlenessand chipping. Such plasticizers are well known to those skilled in theart, and exemplary types of suitable plasticizers for use incompositions of the present invention include organic phthalates,adipates and phosphates. Particular plasticizers suitable for use in thecompositions of the present invention include sucrose diacetatehexa-isobutyrate, glyceryl tribenzoate, tricresyl phosphate, dibutylphthalate, butyl benzyl phthalate, butyl phthalyl, butyl glycolate,dioctyl phthalate, triphenyl phosphate, dibutoxy ethyl phthalate,camphor, castor oil, benzyl benzoate, tributyl phosphate, butyl acetatericenoleate, butyl stearate, triethyl citrate, dibutyl tartrate, diamylphthalate, phosphoinositides and lysophosphatides. The amount ofplasticizer, if used, is from about 0.5 percent to about 30 percent byweight, preferably of from about 1 percent to about 20 percent byweight, and more preferably from about 2 to about 10 percent by weight.

One or more solvents can be used to facilitate suspension of solidcomponents in nail coating formulations ("The Nails", supra, pp369-393). The solvents are preferably non-aqueous. Such solvents arewell known to those skilled in the art, and exemplary types of solventscompatible with the formulations of the present invention includealkanes, alkanols, ketones, esters including acetates, amides, ethers,alcohols, glycol-ethers and nitroparaffins. Specific examples of thesetypes of solvents include ethyl ether, petroleum ether, methyl acetate,acetone, cyclohexane, ethyl acetate, methyl ethyl ketone, carbontetrachloride, ethyl alcohol, n-butyl acetate, isobutyl acetate, amylacetate, xylol, isopropyl alcohol, butyl alcohol, diethylene glycolmonomethylether, diethylene glycol monoethylene ether and ethyl lactate.Also suitable as solvents are acyclic aliphatic and cycloaliphaticcompounds. As noted, aldehydes and ketones are not preferred for use assolvents in the compositions of the present invention. The amount ofsolvent present in the nail coating compositions can be from about 10percent to about 80 percent by weight, preferably from about 15 percentto about 60 percent by weight, and more preferably from about 38 percentto about 50 percent by weight. When alcohols are used as solvents, it ispreferred that the solvent include one or more alcohols in combinationwith one or more non-alcoholic solvents. For example, a suitable solventcan advantageously comprise one or more alcohols, especially isopropylalcohol, and one or more esters, such as butyl acetate and/or ethylacetate. Generally, it is preferred that the amount of alcohol be lessthan about 20 percent by weight, more preferably less than about 15percent by weight, based on the total weight of the composition.

Furthermore, it will be appreciated by those skilled in the art thatcertain solvents can also function as plasticizers, thereby eliminatingthe need to use a separate plasticizer component. Whether or not aplasticizer is needed in the presence of a given quantity and type ofsolvent can readily be determined by one skilled in the art with minimalexperimentation. Solvents that can also function as plasticizersinclude, but are not limited to, methyl acetate, ethyl acetate, n-butylacetate, methyl ether, petroleum ether, cyclohexane, methyl-ethylketone, carbon tetrachloride, ethyl alcohol, isopropyl alcohol, n-butylalcohol, diethylene glycol monoethyl ether, diethyleneglycol monomethylether, and xylol. Other compounds suitable as solvents will be apparentto those skilled in the art.

If desired, one or more diluents can be used to improve stabilization ofviscosity, and to control the overall cost of the formulation. Examplesof compounds that are useful as diluents in formulations of the presentinvention include alcohols, aromatic hydrocarbons and aliphatichydrocarbons. Specific examples of suitable diluents include ethanol,butanol, isopropanol, toluene and xylene. Suitable concentration rangesof diluents for use in compositions of the present invention are fromabout 1 percent to about 80 percent by weight. preferably from about 5percent to about 60 percent by weight and more preferably from about 10percent to about 50 percent by weight. As noted, formulations of thepresent invention preferably exclude toluene and formaldehyde. However,formulations containing toluene and/or formaldehyde are within the scopeof the present invention. If present, the amount of formaldehyde incompositions of the present invention is preferably from 0.1 percent byweight to about 10 percent by weight, preferably from about 0.5 percentto about 7.5 percent by weight, and more preferably from about 2 percentto about 5 percent by weight. Examples of toluene-free andformaldehyde-free embodiments of the present invention are providedbelow.

Pigments and other coloring agents can be used for enhancement of theesthetic qualities of embodiments of the present invention. Colors andpigments useful in nail coating compositions are well known to thoseskilled in the art. Compiled lists of such components are available fromthe United States Food and Drug Administration. Examples of suitablecoloring agents for use in compositions of the present invention includethe insoluble lakes and colored polymeric material, opacity regulatingagents such as titanium dioxide, aluminum silicate, tinting agents suchas iron oxide, and pearlescent agents such as guanine bismuthoxychloride. Specific examples of pigments compatible with compositionsof the present invention include D&C Red 6, D&C Red 30, D&C Red 36, D&CRed 9, D&C Red 7, FD&C Yellow 5, and FD&C Yellow 6.

The amount of pigment used in a nail coating composition such as acolored lacquer can vary, but generally does not exceed about 15 percentby weight, based on the total weight of the composition. For improvedwear resistance, the pigment concentration in nail coatings should notbe lower than about 3 percent by weight. In compositions of the presentinvention, the amount of pigments and/or other coloring agents, if thecoloring agents are pearlescent, is preferably from about 0.05 percentto about 6 percent by weight, more preferably from about 0.1 percent toabout 5.5 percent by weight, and still more preferably from about 0.5percent to about 5 percent by weight. Suitable amounts of pearlescentcomponents range from about 0.5 percent to about 15 percent by weight,preferably from about 1 percent to about 12.5 percent by weight and morepreferably from about 2 percent to about 11 percent by weight.

If desired, compositions of the present invention can be preparedwithout pigments or coloring agents. Such colorless antimicrobial nailcompositions are suitable for use as, for example, basecoats or topcoatswhen used with pigmented nail coatings, or can be used alone.

Ultraviolet (UV) light-absorbing agents can be used in the compositionsof the present invention to inhibit photolysis of susceptible chemicalcompounds and thereby minimize concomitant discoloration of the finishedformulation (Wilkinson, J. B., and Moore, R. J., Eds. "The Nails",supra). Any suitable UV blocker, or combination of blockers, commonlyused in non-aqueous nail coating formulations can be used in thecompositions of the present invention. Specific examples includebenzophenone and derivatives thereof, and FD&C and D&C colors known toabsorb UV radiation. The amount of UV absorbing agent in compositions ofthe present invention can range from about 0.01 percent to about 2percent by weight, preferably from about 0.05 percent to about 1 percentby weight, and more preferably from about 0.06 to about 0.5 percent byweight.

Suspension and/or viscosity regulating agents can be used to facilitatethe ease of application of the compositions of the present invention,and to improve uniformity of flow. Appropriate suspension agents includedimethyl dioctadecyl ammonium bentonite, benzyl dimethyl hydrogenatedtallow ammonium montmorillonite, and dimethyl dioctadecyl ammoniumhectorite. Appropriate viscosity regulating agents that may be usedinclude fused silica and pulverized glass. The amount ofsuspension/viscosity regulating agents used can be from about 0.05percent to about 10 percent by weight, preferably from about 0.2 percentby weight to about 7 percent by weight, and more preferably from about 1percent to about 4 percent by weight. If desired, in addition to orinstead of the above-mentioned compounds, the viscosity may be furtherregulated through the addition of polyvalent acids, such asorthophosphoric acid, in an amount from about 0.05 percent to about 7percent by weight, preferably from about 0.25 percent to about 6 percentby weight and more preferably from about 0.5 percent to about 2 percentby weight.

If desired, the compositions of the present invention can includevitamins, proteins and growth promoters, either alone or in combination.Exemplary suitable vitamins include lipid soluble vitamins, such as thetocopherols, phytonadione, menaquinone, menadione, retinol,3-dehydroretinol; and various amphiphylic water soluble vitamins, suchas cholecalciferol. Other optional components include amphiphylic aminoacids and peptides compatible with the compositions of the presentinvention. Also suitable are agents that are known to promote the growthof fibroblasts and keratinocytes and are compatible with thecompositions of the present invention, such as the phosphatidates, andlyso- derivatives such as lysophosphatidic acid. Vitamins, proteins andgrowth promoters, as a group, can be present in the compositions of thepresent invention in amounts from about 0.001 percent to about 5 percentby weight, preferably from about 0.01 percent to about 3 percent byweight, and more preferably from about 0.05 percent to about 2 percentby weight.

Drying accelerators are commonly used to speed up the drying process ofnail coating formulations, as discussed in U.S. Pat. No. 5,045,309.Hydrocarbons that are compatible with the present invention, and thatcan be used to decrease the overall drying time of nail coatingcompositions according to the invention include the halogenatedhydrocarbons, specifically trichlorotrifluoroethane. Suitableconcentrations of the optional drying accelerators are from about 10percent to about 50 percent by weight, preferably from about 2 percentto about 40 percent by weight, and more preferably from about 30 percentto about 37 percent by weight.

If desired, drying and hardening accelerators can be used to acceleratethe process of hardening agents used in nail coating formulations.Hardening accelerators suitable for use in the compositions of thepresent invention include ultraviolet light-activated curingcompositions such as those described in U.S. Pat, Nos. 5,118,495 and5,516,509, and heat-activated curing compositions. Light-activatedaccelerators generally contain one or more photoinitiators such asalkyl- and heterocyclic-phenyl ketones, and one or more photoreactivemonomers, such as methacrylic acid esters including methyl methacrylate.Photoinitiators can be used in amounts from about 0.05 percent to about10 percent by weight, preferably from about 2.5 percent to about 8percent by weight, and more preferably from about 3 percent to about 5percent by weight. Photoreactive monomers can be used in amounts fromabout 40 percent to about 80 percent by weight, preferably from about 45percent to about 60 percent by weight, and more preferably from about 50percent to about 55 percent by weight. Examples of components used inheat activated curing compositions that can be included in compositionsof the present invention include methyl ethyl ketone, methacrylateester, and hydroxyhydrocinnamate ester, alone or in conjunction withaliphatic esters. Concentrations of heat-activated curing compositionsfor the present invention can range from about 0.05 percent to about 10percent by weight, preferably from about 2.5 percent to about 8 percentby weight, and more preferably from about 3 percent to about 5 percentby weight.

Lipids can be included in the compositions of the present invention.Lipids are important to the functioning of the nail plate as a barrier.However, lipids can be stripped from the nail by organic solventsnormally used in nail care preparations. It is known that lipids can beapplied to dried, hardened nail coatings and can enhance the shine ofthe coatings. However, it has been discovered in connection with thepresent invention that lipids can be incorporated directly into nailcoating compositions. The presence of lipids in nail coatingcompositions can help to ameliorate the depletion of lipids from thenail. Furthermore, while it is not intended that the present inventionbe bound by any particular theory, it is believed that lipidsincorporated into nail coating compositions can diffuse from theinterior of the nail coating to the air/coating surface and/or thenail/coating surface over time, thus continuing to enhance shine andprovide benefits to the nail.

Generally, any lipids compatible with the compositions of the presentinvention can be used. Suitable lipids are well known to those skilledin the art. Exemplary suitable lipids for use in the compositions of thepresent invention include phospholipids, such as phosphatidylcholine,phosphatidylinositol, phosphatidyl serine and phosphatidylethanolamine,lysophospholipids such as lysophosphatidic acid, fatty acids,cholesterol, cholesterol esters, waxes, squalene, triglycerides andsphingolipids. In particular, suitable sphingolipids include ceramidesphingosine, sphingomyelin, and glycolipids including cerebrosides. Ifpresent, the concentration of lipids in compositions of the presentinvention can be from about 0.001 weight percent to about 2 weightpercent, preferably from about 0.001 to about 1 weight percent, and morepreferably from about 0.01 to about 0.5 weight percent. If desired, oilscan be included in the compositions of the present invention. Forexample, tea tree oil is compatible with the compositions of theinvention and can be used therein. Also suitable are one or moreindividual components of tea tree oil, such as terpinen-4-ol, alphaterpineol, alpha pinene, and combinations thereof with or without teatree oil. Such components can be derived from natural sources, or can besynthesized using methods known to those skilled in the art. Oils can bepresent in an amount from about 0.01 weight percent to about 20 weightpercent, preferably from about 0.05 weight percent to about 5 weightpercent, and even more preferably from about 0.1 weight percent to about3 weight percent.

Lipid and/or water soluble vitamins can also optionally be included inthe nail coating compositions of the present invention. These vitaminsare nutrients needed by the cells of the nail matrix that are involvedin the production of keratin and the formation of new nail plate tissue.In particular, lipid soluble vitamins are particularly compatible withthe nail coating compositions of the present invention. Suitable lipidsoluble vitamins for use in the nail coating compositions includevitamins A, E, K, H and D. Particularly useful are vitamin D, andanalogs or precursors thereof, which play a significant role inkeratinization of the nail matrix cells. Exemplary suitable vitamin Dprecursors include ergosterol, 7-dehydrocholesterol, calciferol,cholecalciferol, calcifediol, calcitrol, α-hydroxycholecalciferol anddihydrotachysterol. Vitamins can be present in the compositions of thepresent invention in concentrations of from about 0.0001 to about 2weight percent, preferably from about 0.001 to about 1 weight percent,and more preferably from about 0.01 to about 0.5 weight percent.

EXAMPLES

The following examples are merely illustrative of the present inventionand should not be considered limiting of the scope of the invention inany way. These examples and equivalents thereof will become moreapparent to those skilled in the art in light of the present disclosureand the accompanying claims.

1. Preparation of nail coating compositions

Nail coating compositions were prepared to demonstrate the effectivenessof an incorporated antimicrobial agent. Composition 1, containing as anantimicrobial agent a USP grade BAC, was compared to Composition 2,which did not contain an antimicrobial agent. The compositions wereprepared according to the following formulations:

    ______________________________________                                        Composition 1                                                                       Component     Percent (by weight)                                       ______________________________________                                          Butyl acetate 30.0                                                            N-amyl acetate 30.0                                                           Dibutylphthalate 3.0                                                          Santolite resin 5.00                                                          Nitrocellulose 15.0                                                           Isopropyl alcohol 16.0                                                        Benzalkonium chloride 1.0                                                     (USP grade)                                                                 ______________________________________                                        Composition 2                                                                       Component     Percent (wt)                                              ______________________________________                                          Butyl acetate 30.0                                                            N-amyl acetate 30.0                                                           Dibutylphthalate 3.0                                                          Santolite resin 5.0                                                           Nitrocellulose 15.0                                                           Isopropyl alcohol 17.0                                                      ______________________________________                                    

The components of each composition were mixed together at roomtemperature in the following manner. Liquid components were combined,into which nitrocellulose was then dissolved. Benzalkonium chloride wasadded and the mixture was stirred until visibly free of any undissolvedsolids. Upon application to nails, the solution dried in less than 2minutes to a flexible, non-brittle coating of acceptable handling andesthetic qualities for a basecoat, with durability consistent withShansky's testing method (Shansky, A. Drug Cosmet. Ind.123(5):46(1978)).

The dried coating was evaluated according to an approved surface carrierdisinfection test (Official Methods of Analysis of the Association ofOfficial Analytical Chemists protocol 991.47: Hard surface carrier testmethod). Cultures of a selected test organism were grown for 24 hours atroom temperature in the appropriate growth medium to a density ofapproximately McFarland standard #10. Sterile glass cylinders (BelcoCat. #2090-S0012) served as carriers. The carriers were coated with thetest Composition 1 or the control Composition 2. They were then allowedto dry at room temperature, and subsequently submerged in 5 ml of thestock culture, and allowed to remain there for 15 minutes.

Carriers treated with Composition 1 (BAC), carriers treated withComposition 2 (no agent) and control carriers (untreated) wereaseptically transferred to sterile, dry Whatman #1 filter paper, andexcess droplets of inoculation medium were removed. The carriers wereallowed to dry at 37° C. for 40 minutes and then aseptically transferredto 5 ml of trypsin soy broth. They were subsequently sonicated for 10minutes in a water bath at 25° C. Tubes containing the sonicatedcarriers were vortexed, and a portion of the medium was plated ontoTrypsin Soy agar plates, and incubated overnight at 37° C. Bacterialgrowth was assessed by counting colonies. The results indicated thattreatment with Composition 1 containing the formulation with BAC causeda significantly greater reduction of bacterial growth than did treatmentwith the non-antimicrobial control Composition 2, as compared withbacterial growth on untreated carriers. Testing results are shown inTable II.

                  TABLE II                                                        ______________________________________                                        Results of antimicrobial quality testing of nail                                coating prepared according to Example 1.                                                                  COLONIES                                          ORGANISM CONDITION REMAINING                                                ______________________________________                                        Candida albicans                                                                             Control        1192                                              ATCC 10231 Composition 2      66                                               Composition 1      20                                                         (BAC)                                                                        Enterococcus fecalis Control >10,000                                          ATCC 49452 Composition 2 >10,000                                               Composition 1     442                                                         (BAC)                                                                        Eschericia coli Control   >1000                                               ATCC 11229 Composition 2      72                                               Composition 1      0                                                          (BAC)                                                                        Pseudimonas Control >10,000                                                   aeruginosa Composition 2     1780                                             ATCC 9027 Composition 1      0                                                 (BAC)                                                                        Salmonella cholerasuis Control   >1000                                        enteriditis Composition 2   >1000                                             ATCC 13076 Composition 1      0                                                (BAC)                                                                        Salmonella cholerasuis Control   >1000                                        typhimurium Composition 2   >1000                                             ATCC 19585 Composition 1      0                                                (BAC)                                                                        Staphylococcus aureus Control >10,000                                         ATCC 6538 Composition 2 >10,000                                                Composition 1     160                                                         (BAC)                                                                      ______________________________________                                    

Example 2

Three nail coating compositions were formulated as follows:

    ______________________________________                                        Solution 1 (BAC)                                                                    Component     Percent (by weight)                                       ______________________________________                                          Toluene 37.39                                                                 Ethyl acetate 32.21                                                           Ethyl alcohol 2.00                                                            Dibutyl phthalate 3.40                                                        Santolite resin 10.0                                                          Nitrocellulose 10.0                                                           BAC (USP) 1.0                                                                 Isopropyl alcohol 4.00                                                      ______________________________________                                        Solution 2 (PCMX)                                                                   Component     Percent (wt)                                              ______________________________________                                          Toluene 37.39                                                                 Ethyl acetate 32.21                                                           Ethyl alcohol 2.00                                                            Dibutyl phthalate 3.40                                                        Santolite resin 10.0                                                          Nitrocellulose 10.0                                                           Parachlorometaxylenol 1.0                                                     (PCMX)                                                                        Isopropyl alcohol 4.00                                                      ______________________________________                                        Solution 3 (Vehicle)                                                                Component     Percent (wt)                                              ______________________________________                                          Toluene 37.39                                                                 Ethyl acetate 32.21                                                           Ethyl alcohol 2.00                                                            Dibutyl phthalate 3.40                                                        Santolite resin 10.0                                                          Nitrocellulose 10.0                                                           Isopropyl alcohol 5.00                                                      ______________________________________                                    

The above formulations were prepared as in Example 2, and formed aflexible, non-brittle coating of acceptable handling and aestheticqualities for a basecoat, topcoat or nail lacquer. Furthermore, when thepolymerized coating was tested according to the approved surface carrierdisinfection test (see above) the preparation caused a significantlygreater reduction of bacteria than did a non-antimicrobial, vehiclecontrol. Solution 1, containing BAC (USP) demonstrated greaterantimicrobial efficacy than did the solution containing the other testantimicrobial, PCMX (Table III).

It should be noted that PCMX is a phenol derivative and BAC is aquaternary amine, and phenol derivatives are expected to be morecompatible with the generally non-aqueous, non polar environment of thecurrent invention. However, it is important to note that BAC, whichwould be expected to be more compatible with an aqueous, polarenvironment, is also stable in the formulation prepared according to thepresent invention, illustrating the wide range of chemical propertiestolerated by the compositions of the present invention, and thecompatibility of the compositions with a large number of antimicrobialactive agents.

                  TABLE III                                                       ______________________________________                                        Comparative antimicrobial test of BAC and PCMX.                                                              Bacteria                                         Organism Condition remaining                                                ______________________________________                                          Serratia marcescens Control >1000                                             ATCC 14756 Vehicle (Soln 3) >1000                                              PCMX Basecoat     16                                                          (Soln 2)                                                                      BAC Basecoat      0                                                           (Soln 1)                                                                   ______________________________________                                        Example 3 (Prophetic)                                                           Formulations containing tea tree oil can be made with or                      without toluene.                                                            ______________________________________                                          Toluene-containing formulation with tea tree oil                                         Toluene    45%                                                     Ethyl acetate 10%                                                             Butyl acetate 10%                                                             Nitrocellulose 15%                                                            Adhesive resin 10%                                                            Isopropanol  7%                                                               Tea Tree Oil  3%                                                            ______________________________________                                        Toluene-free formulation with tea tree oil                                             Ethyl acetate                                                                            25%                                                         Butyl acetate 20%                                                             Isopropanol 25%                                                               Nitrocellulose 15%                                                            Adhesive resin 10%                                                            Tea Tree Oil  5%                                                            ______________________________________                                    

What is claimed is:
 1. A method for treating a microbial infection ofthe nail plate comprising applying to the nail a non-aqueousantimicrobial nail coating composition comprising:(a) from about 5percent to about 65 percent by weight of a film-forming polymer; (b)from about 10 percent to about 80 percent by weight of an organicsolvent; and (c) from about 0.05 percent to about 5 percent by weight ofan antimicrobial agent, wherein said antimicrobial agent comprisessolubilized benzalkonium chloride;wherein the benzalkonium chloride (1)is capable of leaching from said nail coating composition followingtransition of the nail coating from a liquid to a solid state followingapplication; (2) retains its antimicrobial activity following (1); and(3) is not inactivated by isopropyl alcohol during storage,wherein allweight percentages are based on the total weight of the nail coatingcomposition.
 2. The method of claim 1 wherein said antimicrobial agentcomprises benzalkonium chloride having the formula ##STR2## wherein R isan alkyl group of from 1 to 24 carbon atoms.
 3. The method of claim 1wherein R is an alkyl group of from 10 to 17 carbon atoms.
 4. The methodof claim 1 wherein said nail coating composition further comprises fromabout 1 percent to about 80 percent by weight of a resin.
 5. A methodfor treating a microbial infection of the nail plate comprising applyingto the nail a non-aqueous antimicrobial nail coating compositioncomprising:(a) from about 1 percent to about 80 percent by weight of aresin; (b) from about 10 percent to about 80 percent by weight of anorganic solvent; and (c) from about 0.05 percent to about 5 percent byweight of an antimicrobial agent, wherein said antimicrobial agentcomprises solubilized benzalkonium chloride;wherein the benzalkoniumcholride (1) is capable of leaching from said nail coating compositionfollowing transition of the nail coating from a liquid to a solid statefollowing application; (2) retains its antimicrobial activity following(1); and (3) is not inactivated by isopropyl alcohol duringstorage,wherein all weight percentages are based on the total weight ofthe nail coating composition.
 6. The method of claim 5 wherein saidantimicrobial agent comprises benzalkonium chloride having the formula##STR3## wherein R is an alkyl group of from 1 to 24 carbon atoms. 7.The method of claim 6 wherein R is an alkyl group of from 10 to 17carbon atoms.